Why lithium works for some and not others


Lithium has long been considered the go-to drug for bipolar disorder, but it is not consistently received by patients. Now they may know why: new research reveals that this is true at the levels of gene activation, especially in the activation or repression of genes which alter the level of apoptosis or cell death. The gene BCL2 which is important to the therapeutic effects of lithium did not increase in the people who did not respond to lithium. A test has been developed to reveal this in the blood of patients within four weeks of beginning treatment.

Testing for gene expression before and after lithium use

The research team from Yale University School of Medicine measured the changing levels of gene activity in twenty depressed patients with bipolar disorder before and after treatment with lithium began.

Many gene levels affected, one most significantly

Over eight weeks of treatment they found definite differences in the levels of gene expression between those who responded to lithium and those who did not. Dr. Robert Beech, research team leader, said, “We found 127 genes that had different patterns of activity (turned up or down) and the most affected cellular signaling pathway was that controlled programmed cell death.”

Gene BCL2 necessary for therapeutic effects

“This positive swing in regulation of apoptosis for lithium responders was measurable as early as four weeks after the start of treatment, while in non-responders there was a measureable shift in the opposite direction. It seems then, that increased expression of BCL2 and related genes is necessary for the therapeutic effects of lithium. Understanding these differences in genes expression may lead towards personalized treatment for bipolar disorder in the future.”

Source: MedicalNewsToday, Biology of Mood & Anxiety Disorders


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